Heart disease, specifically coronary artery disease, is a major cause of death, disability, and healthcare expense in the United States and other industrialized countries. Until recently, most heart disease was considered to be primarily the result of a progressive increase of hard plaque in the coronary arteries. This atherosclerotic disease process of hard plaques leads to a critical narrowing (stenosis) of the affected coronary artery and produces anginal syndromes, known commonly as chest pain. The progression of the narrowing reduces blood flow, triggering the formation of a blood clot (thrombus). The clot may choke off the flow of oxygen-rich blood (ischemia) to heart muscles, causing a heart attack. Alternatively, the clot may break off and lodge in the vessel of another organ, such as the brain, resulting in a thrombotic stroke. Within the past decade, evidence has emerged changing the paradigm of atherosclerosis, coronary artery disease, and heart attacks. While the buildup of hard plaque may produce angina and severe ischemia in the coronary arteries, new clinical data suggest that the rupture of vulnerable plaques, which are often non-occlusive, per se, causes the vast majority of heart attacks. The rate is estimated as high as 60-80 percent.
In many instances, vulnerable plaques do not impinge on the vessel lumen; rather, much like an abscess, they are ingrained within the arterial wall. The majority of vulnerable plaques include a lipid pool, smooth muscle (endothelial) cells, and a dense infiltrate of macrophages contained by a thin fibrous cap. The lipid pool is believed to be formed as a result of pathological process involving low density lipoprotein (LDL), macrophages, and the inflammatory process. The macrophages oxidize the LDL, producing foam cells.
The macrophages, foam cells, and associated endothelial cells release various substances, such as tumor necrosis factor, tissue factor, and matrix proteinases, which result in generalized cell necrosis and apoptosis, pro-coagulation, and weakening of the fibrous cap. The inflammation process may weaken the fibrous cap to the extent that sufficient mechanical stress, such as that produced by increased blood pressure, may result in rupture. The lipid core and other contents of the vulnerable plaque may then spill into the blood stream, thereby initiating a clotting cascade. The cascade produces a blood clot that potentially results in a heart attack and/or stroke. The process is exacerbated due to the release of collagen and plaque components (e.g., collagen and tissue factor), which enhance clotting upon their release.
Various methods of identifying vulnerable plaques have been proposed. These include sensing the temperature differential between healthy vascular tissue and the inflamed tissue of a vulnerable plaque. Devices that identify vulnerable plaques by the higher temperature of the inflamed tissue have been described in, for example, U.S. Pat. No. 5,924,997 to Campbell and U.S. Pat. No. 6,475,159 to Casscells, et al. A spectrographic identification method for vulnerable plaques is described in U.S. Pat. No. 6,475,210 to Phelps, et al.
Currently there are few strategies for reliably treating vulnerable plaques. Percutaneous transluminal coronary angioplasty (PTCA), which is commonly used to treat hard plaques, is contraindicated. In this procedure, a catheter having an inflatable balloon at its distal end is introduced into the coronary artery, and the balloon is inflated to flatten the hard plaque against the arterial wall. Inflation of a balloon catheter near a vulnerable plaque could rupture the thin fibrous cap covering the lipid pool, resulting in precisely the clotting cascade that treatment would seek to prevent. However, radiation treatment, which has been used to prevent the restenosis that sometimes occurs following PTCA, holds promise in treating vulnerable plaques.
While high levels of radiation inhibit stenosis, lower levels appear to promote cell growth and encourage restenosis. For example, hyperplasia has been seen to occur at the distal and proximal edges of a treated area due to reduced radiation exposure at these edges. The resulting stenosis at either end of the treated area is termed a “candy-wrapper” effect.
Thickening of the inner wall of a vessel is clearly an unwanted and deleterious side effect when treating hard plaques. However, such thickening could have a positive effect when it serves to strengthen the thin fibrous cap found atop a vulnerable plaque lesion. With the lesion thus stabilized, time is provided for the use of statin drugs or other agents to shrink or remove the lipid pool.
Radiation therapy can be accomplished in a variety of ways, as discussed, for example, in U.S. Pat. No. 5,213,561 to Weinstein et al., U.S. Pat. No. 5,484,384 to Fearnot, and U.S. Pat. No. 5,503,613 to Weinberger. Among other radiation therapy devices, these references disclose a guide wire having a radioactive tip, a radioactive source within a balloon catheter, and a radioactive source mounted on a balloon expansible stent. In U.S. Pat. No. 6,377,846 B1, Chornenky et al. disclose an improved device for delivering localized x-ray radiation and a method for fabricating such a device.
It would be desirable to have a method of treating vulnerable plaques that overcomes the clear disadvantages of traditional methods of plaque treatment such as PTCA, while realizing the benefits of radiation therapy.